The formation of iminyl radicals from a range of precursors, including hydrazone imines and oxime ethers, under FVP conditions is well documented in the literature.1 Once formed, the iminyl radical can undergo cyclisation onto various aromatic ring systems including phenyl rings, thiophenes and furans to form new fused aromatics.2 The aim of this thesis was to expand the scope of cyclisation of iminyl radical onto pyrrole-type rings and 2-azole rings, generating novel heterocyclic cores via pyrolysis of the corresponding oxime ether precursors. In addition, the cyclisation of iminyl radicals onto C-C double bonds was investigated and afforded isoquinolines shown in Scheme II, providing a new way to synthesise these heterocyclic cores. Mechanistic predictions were supported by DFT calculations in which the thermodynamics and kinetics of the systems were established and the products of iminyl cyclisation reactions were characterised using a range of 2D NMR experiments.

No description available.

The work described in this thesis investigates the mechanisms by which copper complexes catalyse the generation of reactive oxygen species (ROS), including the highly reactive hydroxyl radical (.OH), and induce oxidative damage to DNA. An ESR study into the copper-Fenton reaction revealed that, in the presence of buffers and other copper chelators, .OH is generated. In contrast, it is suggested that a Cu(III) species may be formed in the reaction of aqueous, unchelated copper ions. The generation of .OH in the copper-Fenton reaction, under biomimetic conditions, was confirmed by analysis of the products formed following the incubation of DNA components with this system. Preferential binding of Cu(II) to guanosine over the other nucleosides was determined and copper redox cycling at GC sites was found to be more facile than at AT sites. Stability constants for the copper complexes with several other biochemically important ligands such as glutathione (GSH), Quin2 and 1,10-phenanthroline (OP) were also measured. The ease of redox cycling for the copper complexes was found to be of the order: OP ~ Quin2 > GSH. However, OP enhanced both the copper-Fenton reaction and copper-induced DNA damage while both GSH and Quin2 were inhibitory. Gel chromatography studies suggested that ternary complex formation occurs between Cu(I)-DNA and both Quin2 and OP. This implies that the ternary complex with OP is more redox active than that with Quin2. Whilst cysteine enhanced copper-mediated DNA damage at early incubation times, it was more protective than GSH and homocysteine at later stages. The effects at early incubation times are attributed to the ease of copper redox cycling in the presence of thiols while the effects over prolonged incubations reflect Cu(II) stabilisation by the respective disulphides or similar products.

Chapter 1 introduces the phenomenon of oxygen toxicity and the central role played by oxygen free radicals, most notably the superoxide radical anion. The technique of spin trapping, whereby reactive free radicals are studied and identified, is then introduced. The synthesis of improved spin traps for superoxide by the preparation of 1-pyrroline 1-oxides bearing a C-3 ester or alkyl halide substituent is then discussed. Chapter 2 describes the preparation of 2-(prop-2-enyl)-aldehydes, 2-dimethoxymethylaldehydes and a 2-phenylthiomethylaldehyde. Bromination of 5,5-dimethyl-1-(prop-2-enyl)-1-pyrroline 1-oxide did not give rise to addition at the C=C double bond but recovery of the nitrone and a hydroxamic acid. Similarly, hydrohalogenation of the alkenyl-nitrone did not lead to addition at the C=C double bond. The preparation and utility of 3-(ethoxycarbonylprop-2-enyl)-5,5-dimethyl-1-pyrroline 1-oxide is then described. Chapter 3 details the preparation of 3-dimethoxymethyl-1-pyrroline 1-oxides. Acid-catalysed deprotection of these nitrone acetals did not result in the formation of the expected 3-aldehydo-5,5-dimethyl-1-pyrroline 1-oxides. Chapter 4 deals with the preparation of 5,5-dimethyl-3-phenylthiomethyl-1-pyrroline 1-oxide. Conversion of the phenylthiomethyl group to an iodomethyl group led to the loss of the nitrone. Chlorination of the nitrone gave 4-methyl-4-nitro-2-phenylthiomethylpentanoic acid. Oxidation of 5,5-dimethyl-3-ethoxycarbonyl-1-hydroxypyrrolidine resulted in the dimeric nitrone 3,3'-bis(ethoxycarbonyl)-5,5,5',5'-tetramethyl-3,3'-bi-1-pyrrolinyl 1,1-dioxide being isolated. Chapter 5 concerns the synthetic utility of α-bromoaldehydes. The preparation of 5,5-dimethyl-3-benzenesulphonyl-1-pyrroline 1-oxide is then described. Alkylation of the nitrone in the presence of sodium hydride with methylbromoacetate gave the C-3 disubstituted nitrone, 3-benzenesulphonyl-5,5-dimethyl-3-methoxycarbonylmethyl-1-pyrroline 1-oxide. Chapter 6 concerns the spin trapping reactions of the nitrones prepared in this thesis. The ESR spectra of the hydrogen atom adducts showed the magnetic non-equivalence of the β-hydrogens owing to the presence of the C-3 substituent. Spin trapping of the <I>t</I>-butoxy radical was found to be stereospecific. Apparent selectivity for the hydroxyl radical was found as no spin adducts were detected with the superoxide radical anion.

No description available.

Protonation and hydrogen bonding effects on the redox properties of verdazyl radicals were investigated. Verdazyls with various substituents at the C3 position were synthesized, including species with no basic site, a basic site distant from the verdazyl heterocycle, a basic site proximal to the verdazyl heterocycle but with strained hydrogen bonding geometry, and a basic site proximal to the verdazyl heterocycle with favourable hydrogen bonding geometry. Treatment of these verdazyls with trifluoroacetic acid resulted in several general changes to their cyclic voltammograms: the oxidation and reduction potentials shifted to higher potentials, with concurrent loss of reversibility of the reduction process due to protonation of the verdazylate anion. These changes were likely a result of intermolecular interactions between the substrate and acidic medium rather than specific protonation or intramolecular hydrogen bonding effects. Acid treatment of the verdazyl with favourable hydrogen bonding geometry resulted in emergence of a new reversible process in the CV that was found to match the oxidation process of the corresponding leuco verdazyl. Attempts to synthesize this leuco verdazyl were successful, however purification was not completed. Spectroscopy of the crude product suggests that it may be stable to air, an uncommon feature in leuco species due to their propensity to be easily oxidized by O2. Preliminary investigations of the potential of verdazyls as alcohol oxidation catalysts were made. Several previously reported and novel species were investigated as stoichiometric and catalytic oxidants akin to nitroxides and phenoxyls. It was found that the verdazyls, verdazylium cations and verdazyl-metal complexes tested did not stoichiometrically or catalytically oxidize alcohols. / Graduate

An introduction is presented to the nature of polarized and non-polarized transient spin resonance signals, produced by flash-photolysis e.s.r., followed by a description of the equipment used for experimental work. Theories of Chemically Induced Dynamic Electron Spin Polarization are reviewed and various models introduced to illustrate these concepts. A description is given of the first thorough investigation into the effect of CIDEP polarization transfer down a free radical chain and expands upon the consequences of hyperfine-dependent relaxation and the relative signs of coupling constants in various radical species. It concludes with an account of two methods of kinetic analysis which are the first practical demonstrations of their kind, and employ extension of expressions developed in earlier chapters. Studies are made of the CIDEP behaviour of radicals in high viscosity paraffins. A reassessment of previous published work is made: anomalous polarization behaviour was found to have been over-compensated for. A new method of extracting values for T₁ and T<sub>2,/sub> is demonstrated for strong transient e.s.r. signals. A collection of experimental data relating to the previously unexplained absorptive polarization observed in the spectrum of ketyl radicals and the longer-time phase inversion of hyperfine-dependent CIDEP is given. The operation of Triplet Mechanism CIDEP in the ketyl radical systems is ruled out and a division of radicals into geminately formed and free-encounter pairs is shown to be incapable of explaining the observed phase changes. In its place a cross-relaxational mechanism, drawing upon simultaneously generated nuclear spin polarization is advanced. Conclusions are drawn that this may account for both anomalies. Lastly a photochemical application of CIDEP is demonstrated; two different reaction intermediates are identified upon photolysis of ortho phthalaldehyde, depending upon the quenching conditions. A reaction scheme consistent with all experimental data is proposed. A brief comment upon the photo-chemistry of indan 2-one concludes this work.

A series of 2,6- and 3,5-ethynylpyridyl compounds and their cobalt clusters have been prepared and analysed in Chapter 2, in order to study through-space and through-bond interactions between the ethynyl arms. Bidentate N- donor ligands, such as bipyridine and o-phenanthroline with alkyne functionality have been used extensively as building blocks for a wide range of molecular materials, but monodentate ethynylpyridyls have received less attention. The results showed that while there is no orbital restriction on a RC[triple bond]C-n-[pi]�cc-C[triple bond]CR through-bond interaction in 2,6-ethynylpyridyls, no significant interaction exists. Nevertheless, there are intramolecular interactions as manifested in the distortions which occur in the solid state structure of the compounds and the lability of the diphenylphosphine methane (dppm) moieties in the oxidised Co₂(CO)₄dppm species. Polymerisation by Sonogashira coupling between dibromo pyridines or diiodo ferrocene and ethynyl pyridines resulted in only oligomeric fractions that could be separated. The thesis also reports the synthesis and characterization of some novel naphthalimide monomers with acrylic and allyl headgroups. The naphthalimide moiety is substituted in the 4-position with various functionalities. This is presented in detail in Chapter 3 of the thesis. The monomers� structure is the following: [illustration omitted] wherein: A may be a polymerizable group (methacrylate or allyl), which includes a spacer entity (aliphatic or aromatic); B is selected from an ethenyl or ethynyl linked organometallic group, a halogen and/or an amine (i.e. bromo, ethynylferrocene, ethenylferrocene, trimethylsilylethynyl, nitro, piperidine and ethenylpiperidine). The acrylic monomers were synthesized by coupling 4-bromo-1,8-naphthalic anhydride with an amino alcohol to give an imide, which then was coupled with methacryloyl chloride to provide the methacrylate. Functionalization in the 4-position of the naphthalimide moieties was achieved by Sonogashira and Heck coupling reactions with for example ethynylferrocene, trimethylsilyl acetylene, vinylferrocene. For the allyl monomers synthesis, a reaction between allyl amine and 4-Bromo-naphthalic anhydride provided 4-bromo-naphthalimido allyl, which was then functionalized by further Sonogashira and Heck coupling reactions. The monomers were polymerised and copolymerised with other widely used comonomers, such as methyl methacrylate, methyl acrylate, styrene, vinyl carbazole and acrylonitrile. The polymerisation processes and the full analyses of the (co)polymers are described in Chapter 4. Free radical polymerisation, FRP, initiated by azo bisisobutyronitrile, AIBN at elevated temperature was the main technique employed for making the (co)polymers. Atom Transfer Radical Polymerisation, ATRP was conducted for some monomers although the results were inconclusive (the yields were low, under 50%, but the molecular weight distributions were quite narrow, PDI�s <1.7). Heck coupling polymerisation was performed for the bromo- substituted methacrylic and allyl monomers and supplied colorful, well-defined polymeric materials, with low polymerisation degrees. All polymers were analyzed by HPLC, NMR, UV-VIS, IR, electrochemistry and fluorescence. The (co)polymers made by FRP had various molecular masses (Mn = 3000- 90.000), whereas the polydispersities were PDI = 1.4- 4.6. Most of the (co)polymers were fluorescent and had good thermal and electrochemical properties. Potential applications of the polymers have been suggested and relevant literature background in the field is provided in both Chapters 1 and 4. The monomers/ polymers are stable compounds (no special storage conditions required) and can act as good candidates for potential applications in light emitting devices, as resins/ binders for coating materials, in the dyes and pigment industry and also for manufacturing of conducting polymers and/or composite materials.

Thesis (MSc)--University of Stellenbosch, 2006. / Bibliography. Also available via the Internet.

Thesis (Ph.D.) -- McMaster University, 1998. / Includes bibliographical references. Also available via World Wide Web.